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microRNA-155, induced by interleukin-1ß, represses the expression of microphthalmia-associated transcription factor (MITF-M) in melanoma cells.

Arts N, Cané S, Hennequart M, Lamy J, Bommer G, Van den Eynde B, De Plaen E - PLoS ONE (2015)

Bottom Line: We previously reported that interleukin-1ß (IL-1ß) can downregulate MITF-M levels.Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma.Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, Brussels and Université Catholique de Louvain, Brussels, Belgium.

ABSTRACT
Loss of expression of surface antigens represents a significant problem for cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M) regulates melanocyte fate by driving expression of many differentiation genes, whose protein products can be recognized by cytolytic T lymphocytes. We previously reported that interleukin-1ß (IL-1ß) can downregulate MITF-M levels. Here we show that downregulation of MITF-M expression by IL-1ß was paralleled by an upregulation of miR-155 expression in four melanoma lines. We confirmed that miR-155 was able to target endogenous MITF-M in melanoma cells and demonstrated a role for miR-155 in the IL-1ß-induced repression of MITF-M by using an antagomiR. Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma. Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation. This could represent a novel mechanism of melanoma immune escape in an inflammatory microenvironment.

No MeSH data available.


Related in: MedlinePlus

In mouse melanoma samples, there is an anti-correlation between the expression of MITF-M or Tyrosinase and that of IL-1ß or miR-155.24 tumor samples were collected from 23 Tirp10B mice [21] and the expression of MITF-M, Tyrosinase, IL-1ß and miR-155 was analyzed by quantitative RT-PCR. ß-actin was used as an internal control for MITF-M, Tyrosinase and IL-1ß whereas U6 was used as an internal control for miR-155. Taken together, our results suggest that the inverse correlation between the expression levels of miR-155 on the one side, and MITF-M and tyrosinase on the other side is also observed in vivo.
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pone.0122517.g006: In mouse melanoma samples, there is an anti-correlation between the expression of MITF-M or Tyrosinase and that of IL-1ß or miR-155.24 tumor samples were collected from 23 Tirp10B mice [21] and the expression of MITF-M, Tyrosinase, IL-1ß and miR-155 was analyzed by quantitative RT-PCR. ß-actin was used as an internal control for MITF-M, Tyrosinase and IL-1ß whereas U6 was used as an internal control for miR-155. Taken together, our results suggest that the inverse correlation between the expression levels of miR-155 on the one side, and MITF-M and tyrosinase on the other side is also observed in vivo.

Mentions: We collected 24 tumor samples from 23 mice and analyzed the expression of MITF-M, tyrosinase, IL-1ß and miR-155 by quantitative RT-PCR using RNA extracted from total tumor tissue. We found that 4 out of 23 samples expressed MITF-M and tyrosinase, did not express IL-1ß and expressed weakly miR-155 (Fig 6). On the other hand, 19 out of 23 melanoma samples did not express MITF-M and tyrosinase or expressed low levels of MITF-M but had high levels of expression of miR-155. All these 19 tumor samples showed expression of IL-1ß to varying degree, suggesting that this cytokine could contribute to the upregulation of miR-155. We should note, however, that other inflammatory cytokines share the downstream signaling cascade with IL-1ß and might very well contribute to the expression of miR-155 in these samples (Fig 6).


microRNA-155, induced by interleukin-1ß, represses the expression of microphthalmia-associated transcription factor (MITF-M) in melanoma cells.

Arts N, Cané S, Hennequart M, Lamy J, Bommer G, Van den Eynde B, De Plaen E - PLoS ONE (2015)

In mouse melanoma samples, there is an anti-correlation between the expression of MITF-M or Tyrosinase and that of IL-1ß or miR-155.24 tumor samples were collected from 23 Tirp10B mice [21] and the expression of MITF-M, Tyrosinase, IL-1ß and miR-155 was analyzed by quantitative RT-PCR. ß-actin was used as an internal control for MITF-M, Tyrosinase and IL-1ß whereas U6 was used as an internal control for miR-155. Taken together, our results suggest that the inverse correlation between the expression levels of miR-155 on the one side, and MITF-M and tyrosinase on the other side is also observed in vivo.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390329&req=5

pone.0122517.g006: In mouse melanoma samples, there is an anti-correlation between the expression of MITF-M or Tyrosinase and that of IL-1ß or miR-155.24 tumor samples were collected from 23 Tirp10B mice [21] and the expression of MITF-M, Tyrosinase, IL-1ß and miR-155 was analyzed by quantitative RT-PCR. ß-actin was used as an internal control for MITF-M, Tyrosinase and IL-1ß whereas U6 was used as an internal control for miR-155. Taken together, our results suggest that the inverse correlation between the expression levels of miR-155 on the one side, and MITF-M and tyrosinase on the other side is also observed in vivo.
Mentions: We collected 24 tumor samples from 23 mice and analyzed the expression of MITF-M, tyrosinase, IL-1ß and miR-155 by quantitative RT-PCR using RNA extracted from total tumor tissue. We found that 4 out of 23 samples expressed MITF-M and tyrosinase, did not express IL-1ß and expressed weakly miR-155 (Fig 6). On the other hand, 19 out of 23 melanoma samples did not express MITF-M and tyrosinase or expressed low levels of MITF-M but had high levels of expression of miR-155. All these 19 tumor samples showed expression of IL-1ß to varying degree, suggesting that this cytokine could contribute to the upregulation of miR-155. We should note, however, that other inflammatory cytokines share the downstream signaling cascade with IL-1ß and might very well contribute to the expression of miR-155 in these samples (Fig 6).

Bottom Line: We previously reported that interleukin-1ß (IL-1ß) can downregulate MITF-M levels.Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma.Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, Brussels and Université Catholique de Louvain, Brussels, Belgium.

ABSTRACT
Loss of expression of surface antigens represents a significant problem for cancer immunotherapy. Microphthalmia-associated transcription factor (MITF-M) regulates melanocyte fate by driving expression of many differentiation genes, whose protein products can be recognized by cytolytic T lymphocytes. We previously reported that interleukin-1ß (IL-1ß) can downregulate MITF-M levels. Here we show that downregulation of MITF-M expression by IL-1ß was paralleled by an upregulation of miR-155 expression in four melanoma lines. We confirmed that miR-155 was able to target endogenous MITF-M in melanoma cells and demonstrated a role for miR-155 in the IL-1ß-induced repression of MITF-M by using an antagomiR. Notably, we also observed a strong negative correlation between MITF-M and miR-155 levels in a mouse model of melanoma. Taken together, our results indicate that MITF-M downregulation by inflammatory stimuli might be partly due to miR-155 upregulation. This could represent a novel mechanism of melanoma immune escape in an inflammatory microenvironment.

No MeSH data available.


Related in: MedlinePlus